NorthWest Biotherapeutics Inc (NWBO)

[skitahoe]

If way back when they were designing this trial they had known all about pseudoprogression does anyone think that it would have been fair to have one third the patients be the control with no opportunity to receive the vaccine. Without being able to use historical data, that would have had to be how the trial was designed with the single goal of overall survival.

The crossover gives the control a possibility of benefit on progression, but where progression can't be differentiated from pseudoprogression it can't work, so control patients would not be permitted to cross over.

I don't like the idea that people who volunteer for a trial are to receive no benefit if they're unlucky enough to be in the one third the patients who would be designated control. If we put 100 people in the control, reliable data would say that no more than 5 of them would live for 5 years.

I believe that if you were designing the trial today it would have all patients receiving the vaccine and survival would be looked at from 2 years out. If sufficient benefits were seen with 2 years of data, the trial could end there, if not another look would be taken at 3, etc. Of course all patients would be a different treatment durations, but ideally all would be enrolled in under a year so by the time the last patient reached a year the first patient would still not yet be at year 3.

This cancer is so deadly that a trial structured in this way could show substantial benefits in a couple years. I believe the company went beyond 5 years because of the confusion caused by pseudoprogression, and because OS was not the primary goal. I believe they've adapted what people can say was a flawed design, but it was only flawed by what they learned during the trial. In the end I don't see how anyone can doubt that the vaccine should be approved.

Gary